1. Ecstasy induces reactive oxygen species, kidney water absorption and rhabdomyolysis in normal rats. Effect of N-acetylcysteine and Allopurinol in oxidative stress and muscle fiber damage
- Author
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Regina Lúcia de Moraes Moreau, Antonio J. Magaldi, Antonio Carlos Seguro, Daniele Canale, Pedro Henrique França Gois, Maria Heloisa Massola Shimizu, Denise A. de Jesus, Ana Maria Gonçalves da Silva, Thales de Brito, and Ana Carolina de Bragança
- Subjects
Male ,Vasopressin ,Physiology ,Muscle Fibers, Skeletal ,HIPERTERMIA INDUZIDA ,lcsh:Medicine ,Pathology and Laboratory Medicine ,medicine.disease_cause ,Kidney ,Biochemistry ,Antioxidants ,Rhabdomyolysis ,Body Temperature ,Acetylcysteine ,chemistry.chemical_compound ,0302 clinical medicine ,Drug Metabolism ,Medicine and Health Sciences ,030212 general & internal medicine ,lcsh:Science ,Solute Carrier Family 12, Member 1 ,chemistry.chemical_classification ,Multidisciplinary ,Ingestion ,Free Radical Scavengers ,Glutathione ,Chemistry ,Physiological Parameters ,Physical Sciences ,Toxicity ,Anatomy ,Research Article ,Chemical Elements ,medicine.drug ,medicine.medical_specialty ,Allopurinol ,N-Methyl-3,4-methylenedioxyamphetamine ,Blotting, Western ,Lithium ,Thiobarbituric Acid Reactive Substances ,03 medical and health sciences ,Signs and Symptoms ,Diagnostic Medicine ,Internal medicine ,medicine ,TBARS ,Animals ,Hyperthermia ,Pharmacokinetics ,Kidney Tubules, Collecting ,Rats, Wistar ,Epithelial Sodium Channels ,Pharmacology ,Reactive oxygen species ,Aquaporin 2 ,urogenital system ,lcsh:R ,Biology and Life Sciences ,Kidney metabolism ,Water ,Correction ,Kidneys ,RIM ,Renal System ,Oxidative Stress ,Endocrinology ,chemistry ,Hallucinogens ,lcsh:Q ,Physiological Processes ,Reactive Oxygen Species ,030217 neurology & neurosurgery ,Oxidative stress - Abstract
Background Ecstasy (Ec) use produces hyperthermia, excessive sweating, intense thirst, an inappropriate antidiuretic hormone secretion (SIADH) and a multisystemic toxicity due to oxidative stress (OS). Intense thirst induces high intake of pure water, which associated with SIADH, usually develops into acute hyponatremia (Hn). As Hn is induced rapidly, experiments to check if Ec acted directly on the Inner Medullary Collecting Ducts (IMCD) of rats were conducted. Rhabdomyolysis and OS were also studied because Ec is known to induce Reactive Oxygen Species (ROS) and tissue damage. To decrease OS, the antioxidant inhibitors N-acetylcysteine (NAC) and Allopurinol (Allo) were used. Methods Rats were maintained on a lithium (Li) diet to block the Vasopressin action before Ec innoculation. AQP2 (Aquaporin 2), ENaC (Epitheliun Sodium Channel) and NKCC2 (Sodium, Potassium, 2 Chloride) expression were determined by Western Blot in isolated IMCDs. The TBARS (thiobarbituric acid reactive substances) and GSH (reduced form of Glutathione) were determined in the Ec group (6 rats injected with Ec-10mg/kg), in Ec+NAC groups (NAC 100mg/Kg/bw i.p.) and in Allo+Ec groups (Allo 50mg/Kg/i.p.). Results Enhanced AQP2 expression revealed that Ec increased water transporter expression, decreased by Li diet, but the expression of the tubular transporters did not change. The Ec, Ec+NAC and Allo+Ec results showed that Ec increased TBARS and decreased GSH, showing evidence of ROS occurrence, which was protected by NAC and Allo. Rhabdomyolysis was only protected by Allo. Conclusion Results showed that Ec induced an increase in AQP2 expression, evidencing another mechanism that might contribute to cause rapid hyponatremia. In addition, they showed that NAC and Allo protected against OS, but only Allo decreased rhabdomyolysis and hyperthermia.
- Published
- 2016